For years, research in cardiovascular medicine has focused on the delivery of nitric oxide (NO) and carbon monoxide (CO), both of which are endogenously produced diatomic signaling molecules. It has been determined that therapies based on the administration of CO and NO protect the brain, heart and circulation against any number of cardiovascular diseases and conditions.
However, several studies have shown that both CO and NO treatments can be less than beneficial to a recipient. Although CO is beneficial for certain therapies, it has been known for decades to be a poisonous chemical in excess as it competes with carbon dioxide (CO2) for preferential binding to hemoglobin in the blood. This preferential binding of CO leads to an excess of CO2 in the blood and a detrimental state for the individual. NO, on the other hand, has been shown to be toxic at high concentrations due to the highly reactive nature of NO and its interaction with superoxide to form the potent oxidant peroxynitrite (ONOO−).
As a result of the two diatomic signaling molecule's acute toxicities, site specific administration has been pursued over the last decade, particularly of NO. Implantable medical devices such as vascular stents have been developed incorporating coatings which can provide controlled release of NO once implanted into a diseased vessel. This site-specific administration of NO avoids the toxicity of a systemic administration, but does not avoid the effects of local ONOO− formation.
Recently, a third endogenously produced signaling molecule, hydrogen sulfide (H2S), has emerged as a candidate for cardiovascular therapy. Studies have shown that H2S may be beneficial for vasodilatation, anti-inflammation, anti-restenosis and therapeutic angiogenesis. See Benavides, et. al., Proc. Nat'l. Acad. Sci. USA, 104: 17977-17982 (2007) and Lefer, Proc. Nat'l. Acad. Sci. USA, 104: 17907-17908 (2007), the contents of which are incorporated herein in their entirety. However, H2S by nature is a toxic gas and, therefore, systemic administration is not a viable means for treating cardiovascular conditions. Therefore, methods of local, site-specific, administration of H2S in order to utilize its vasodilating, anti-inflammation, anti-restenotic and therapeutic angiogenic properties would be highly beneficial.